Multiple sclerosis treatment only focuses on recurrence and disability progression?

*Only for medical professionals to read for reference.
Focus on brain atrophy and start DMT early
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 When it comes to multiple sclerosis (MS), what do you think of? Perhaps many people's answers will be rare diseases, inflammation, recurrence, disability.
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and few people mention brain atrophy
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 But the fact is that there are no obvious symptoms in the early stage of MS, but brain atrophy may have occurred at this time, and it can accompany the entire course of the disease
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 Increasing attention to brain atrophy has become an important research endpoint of MS.
In the past, we usually believed that the pathological mechanism of MS was inflammatory or immune demyelination.
Severe axon loss and brain atrophy were the manifestations in the later stage of MS; The pathological data also emphasizes that brain atrophy is a reflection of the final stage of the disease
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However, many studies have shown that measurable brain atrophy has occurred in the early stages of MS [1,2]
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 According to the research progress of MR imaging and histopathology, MS lesions are currently classified as acute active lesions, chronic active lesions (slow dilation/smoldering lesions) and chronic inactive lesions [3]
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Both acute focal injury and chronic diffuse injury are related to the loss of MS function [4], however, acute focal inflammation cannot fully explain the brain end organ damage seen in MS and the resulting disability and cognitive deterioration [5]; and chronic active disease (smoldering focus) seems to be the driving factor of persistent neurodegeneration [6]
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Studies have shown that chronic smoldering lesions cause brain volume loss, which is more related to disability and cognitive impairment in MS patients [7,8]
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 Figure 1: The loss of brain volume caused by chronic smoldering lesions.
With the increasing number of related studies, brain atrophy has been accepted as an effective, sensitive and reproducible evaluation index for MS neurodegeneration; at the same time, published in Nature Reviews Neurology in 2020 ( The MS Magnetic Resonance Imaging Multi-Center Collaborative Research Network (MAGNIMS) consensus on impact factor 42.
937 recommends the use of whole brain atrophy (at least 12 months as a cycle) as the secondary or even primary endpoint of MS clinical trials to evaluate the effects of drugs on the disease The role of related neurodegenerative changes
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At present, reducing brain volume loss (BVL) has been a key research endpoint, and more are included in clinical trials of disease-modifying therapy (DMT) drugs.
The importance of brain atrophy has been widely recognized [9,10]
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 Figure 2: MAGNIMS recommends that brain volume loss is an important indicator for the evaluation of MS.
The importance of brain atrophy is becoming more and more prominent.
What impact will it have on patients? Any incident has its own reasons behind it
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With the deepening of research on MS brain atrophy, more and more data show that brain atrophy can have multiple effects on patients and can be used as a predictor of disease progression
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 ■ The greater the loss of brain volume, the higher the risk of disability progression.
At present, many studies have evaluated and explored the relationship between brain atrophy and disability progression in MS patients
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The TEMSO study grouped patients according to the proportion of BVL at 2 years, and analyzed the relationship between brain volume loss at 2 years and changes in the Extended Disability Status Scale (EDSS) score
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The results showed that patients with more brain volume loss in the early stages of the disease had a significantly higher risk of long-term disability progression.
Compared with patients in the highest BVL group, patients in the lowest BVL group had a significantly lower risk of disability progression by 42% in the 7th year [11]
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 Figure 3: The risk of disability progression in different BVL groups over time.
Some clinicians and patients may attribute the disability progression of MS to the recurrence of the disease.
In fact, prospective studies have shown that there is no recurrence except for the disability progression caused by recurrence.
The related continuous loss of brain volume was significantly correlated with the progression of disability (P=0.
0009) [12]
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 ■ Decreased cognitive function? Checking the brain atrophy.
MS can not only cause physical disability in patients, but also often cause different degrees of cognitive impairment
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It is generally believed that the incidence of cognitive impairment in different forms and degrees of MS is about 45%-65%.
The occurrence and severity of cognitive dysfunction in MS is not significantly related to physical disability, while the degree of brain atrophy is directly related to cognitive impairment.
In connection, the greater the degree of brain atrophy, the more severe the cognitive impairment of MS patients [13-15]
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 An 8-year retrospective longitudinal observational study evaluated the relationship between cognitive impairment and disease progression
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The results show that compared with patients with normal cognitive function, patients with mild and severe cognitive impairment have significantly greater changes in the thickness of the whole cerebral cortex [13]
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The cause of brain atrophy is due to neurodegenerative changes, which leads to the occurrence of cognitive impairment.
Therefore, starting DMT as soon as possible to improve brain atrophy can further improve cognitive dysfunction
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Figure 4: The correlation between cognitive function and changes in the thickness of the whole brain cortex ■ Early attention to brain atrophy to reduce the risk of disease conversion.
In the phase III clinical study TOPIC, brain atrophy and the conversion of clinically isolated syndrome (CIS) to clinically diagnosed MS were discussed (CDMS) The relationship between risks
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The results show that compared with the group with the highest total brain atrophy, the group with the least total brain atrophy has a 58% reduction in the risk of switching to CDMS within 1-2 years, and a 29% reduction in the risk of switching to CDMS within 1-5 years [16].
Reducing the rate of brain volume loss in the early stage of the disease can further delay the conversion of CIS patients to CDMS
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 Figure 5: The relationship between the percentage of brain volume change and MS conversion in CIS patients (*P <0.
001) Peripheral + central dual-pronged approach, teriflunomide can effectively reduce the risk of brain atrophy in patients.
There is evidence that MS patients have undergone the first clinical symptoms The longer the delay in hospital visits, the more severe the initial disability of the brain and other parts [17]
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Therefore, DMT should be activated as soon as possible to maximize brain health
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 Teriflunomide has both peripheral anti-inflammatory and central protective functions.
In the central nervous system (CNS), studies have shown that teriflunomide can cross the blood-brain barrier and reach clinically relevant concentrations in the CNS.
Activation has an inhibitory effect, reducing the proliferation of oligodendrocytes and promoting remyelination, thereby delaying brain atrophy [18]
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A number of studies have confirmed that teriflunomide can significantly reduce the risk of brain atrophy in patients
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 Radue et al.
[19] analyzed 969 follow-up MRI images in the TEMSO study (baseline patient N=801).
After evaluating the effect of teriflunomide on the degree of brain volume atrophy in patients with relapsing MS, they found that 1 year from baseline At and 2 years, teriflunomide reduced the patient's risk of brain volume atrophy by 36.
9% (P=0.
0001) and 30.
6% (P=0.
0001), respectively
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This result is consistent with the clinical effect of teriflunomide in delaying the deterioration of disability
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 Figure 6: Average annual changes in brain volume during 1 or 2 years of teriflunomide treatment.
Zivadinov et al.
[20] conducted an extended analysis of the data from the phase III TOPIC study, and maintained the original dose in patients receiving teriflunomide treatment in the core study Treatment; and patients receiving placebo were reassigned to teriflunomide 7 mg or 14 mg treatment at a ratio of 1:1, and the brain volume of the patients was evaluated in the first 1-2 years
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 The results showed that in the first 1-2 years, compared with the placebo group, 14 mg teriflunomide treatment can significantly reduce the patient's annual cortical gray matter (CGM) and whole brain (WB) atrophy [% reduction: 12th Month, 61.
4% (CGM; P=0.
0359) and 28.
6% (WB; P=0.
0286); 24th month, 40.
2% (CGM; P=0.
0416) and 43.
0% (WB; P< 0.
0001)]
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 Figure 7: The effect of teriflunomide WB volume.
Sprenger et al.
[21] divided the PBVC of patients treated with teriflunomide in the core phase of the TESMO study into 3 groups, and the PBVC of patients in the placebo group from baseline to 2 years of follow-up was used as the standard: Group 1-BVL is the least; Group 2-BVL is moderate; Group 3-BVL is the most
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To analyze the changes in Z-scores of patients treated with teriflunomide during the extended period of the continuous additive auditory test (PASAT-3)
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The results showed that patients with less brain volume loss after teriflunomide treatment had significant improvement in cognitive function
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 Figure 8: Comparison of the core study baseline, changes in PASAT-3 Z-score, classified by PBVC group Summary MS is a chronic progressive disease.
As the disease progresses, patients will experience disease onset, disability progression, and brain atrophy.

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Among them, brain atrophy is closely related to the progression of disability, and can predict the subsequent disease process of patients.
In addition, brain atrophy can also significantly affect the cognitive function of patients.
Therefore, brain atrophy has also received more and more attention in recent years
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Teriflunomide is a first-line treatment recommended by domestic and foreign guidelines.
It can effectively inhibit the brain atrophy of MS patients through the dual effects of peripheral + central, thereby improving the cognitive function of patients
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Experts comment that in clinical practice, 80%-85% of MS patients are of relapsing-remitting type.
This stage usually manifests as an obvious recurrence and remission process.
The patients basically recover after each symptom onset, leaving no or only minor sequelae
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However, non-clinical recurrence does not mean that the disease does not progress.
Under the clinical appearance, brain atrophy is continuously progressing, which seriously affects the patient's behavioral ability and cognitive function
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 In recent years, with the deepening of MS research, more and more researchers and clinicians have begun to pay attention to the chronic progress of MS, and its most important imaging-related index brain atrophy has been included in the key research endpoints of MS
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In a practical environment, we should make full use of MRI and other methods to systematically evaluate patients' brain atrophy on a regular basis
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At the same time, when making treatment decisions, it is also necessary to comprehensively consider the effect of treatment options on delaying brain atrophy
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Teriflunomide is a first-line DMT drug unanimously recommended by domestic and foreign guidelines.
It is widely used in clinical practice.
Teriflunomide has both peripheral anti-inflammatory and central protection functions, especially in the central nervous system.
It can be delayed by affecting glial cells.
Brain atrophy.
At present, its efficacy in reducing brain atrophy has been confirmed in a number of clinical trials
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Expert profileProfessor Huang Dehui, Chief Physician, Chief Physician, Neuroimmunology Subspecialty, First Medical Center, PLA General Hospital Critical disease clinical and basic research Member of the Neuroimmunology Group of the Neurology Branch of the Chinese Medical Association Standing Member of the Neuroimmunology Branch of the Chinese Society of Immunology Member of the Neuroimmunology Group of the Neurology Branch of the Chinese Medical Association Member of the Standing Committee of the Critical Cerebrovascular Disease Professional Committee of the Health and Family Planning Commission, "Chinese Journal of Neuroimmunology and Neurology" Member of the editorial board, participating in key military projects, Wu Jieping Foundation, National High-Tech Research and Development Program (863), National Science and Technology Support Program (973) and other key research subjects; was the target of cultivation of the "Magic Formula for All Diseases" of the General Hospital of the People's Liberation Army
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Write the "Chinese Expert Consensus on the Diagnosis and Treatment of Multiple Sclerosis" and "Guidelines for the Diagnosis and Treatment of Neuromyelitis Optician Spectrum Diseases"
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In 2014, the "Serial Research on Demyelination-Related Diseases" won the second prize of Army Scientific and Technological Achievements
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In 2018, "Research on Tumor-like Demyelinating Lesions" won the second prize of Beijing Medical Science and Technology
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[21]Sprenger T et al.
AAN 2018, poster P372.
[MAT-CN-2132611, valid until December 29, 2023] This number is only for Sanofi’s reference to this article The confirmation of the authenticity of the scientific and clinical data sources in the therapeutic field of Sanofi-related drugs involved does not serve as Sanofi’s confirmation and guarantee for the accuracy, timeliness and completeness of all the contents of this article; this article is for medical and health professionals only Use by people for academic exchanges or understanding medical information does not constitute the recommendation and promotion of any medicine or treatment plan2020 Nov 11;13:1756286420970754.
[21]Sprenger T et al.
AAN 2018, poster P372.
[MAT-CN-2132611, valid until December 29, 2023] This serial number is only for Sanofi’s reference to this article The confirmation of the authenticity of the scientific and clinical data sources in the therapeutic field of Sanofi-related drugs shall not be used as Sanofi’s confirmation and guarantee of the accuracy, timeliness and completeness of all the contents of this article; this article is only for medical and health professionals for academics Use for the purpose of communicating or understanding medical information does not constitute the recommendation or promotion of any drug or treatment plan2020 Nov 11;13:1756286420970754.
[21]Sprenger T et al.
AAN 2018, poster P372.
[MAT-CN-2132611, valid until December 29, 2023] This serial number is only for Sanofi’s reference to this article The confirmation of the authenticity of the scientific and clinical data sources in the therapeutic field of Sanofi-related drugs shall not be used as Sanofi’s confirmation and guarantee of the accuracy, timeliness and completeness of all the contents of this article; this article is only for medical and health professionals for academics Use for the purpose of communicating or understanding medical information does not constitute the recommendation or promotion of any drug or treatment plan
.

The information contained in this article should not replace medical advice provided by healthcare professionals
.

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